title: Downregulation of CD40 ligand response in monocytes from sepsis patients.
abstract: It has been suggested that a defective adaptive immune response contributes to septic immunosuppression. Here, the response of monocytes to CD40 ligand (CD40L) for patients with sepsis due to infection with gram-negative organisms has been analyzed. Compared to cells from controls, monocytes from septic patients showed significantly reduced production of tumor necrosis factor alpha, interleukin-1beta (IL-1beta), and IL-12 and were unable to acquire high levels of CD80 and CD86 molecules. These alterations were observed at the onset of sepsis and persisted at day 7. However, the ability of monocytes to respond to CD40L stimulation was partially but significantly restored in cells from patients who recovered from sepsis. In addition, costimulation of autologous CD4+ T lymphocytes by CD40L-activated monocytes from septic patients failed to induce cell proliferation and gamma interferon production. Finally, the ability of CD40L to rescue monocytes from apoptosis was severely impaired. We conclude that downregulation of the CD40L response may be an appropriate model for the monocyte alteration observed during septic immunosuppression and may help in the development of novel therapeutic strategies.
authors.affiliation: Department of Public Health and Cellular Biology, Intensive Care Unit, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Sinistro
authors.forename: Cristiana
authors.initials: C
authors.lastname: Almerighi
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciaprini
authors.forename: Silvia
authors.initials: S
authors.lastname: Natoli
authors.forename: Emanuele
authors.initials: E
authors.lastname: Sussarello
authors.forename: Sara
authors.initials: S
authors.lastname: Di Fino
authors.forename: Francesca
authors.initials: F
authors.lastname: Calò-Carducci
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rocchi
authors.forename: Alberto
authors.initials: A
authors.lastname: Bergamini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D018805:Sepsis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D018664:Interleukin-12